Src tyrosine kinase is a novel direct effector of G proteins

Cell. 2000 Sep 1;102(5):635-46. doi: 10.1016/s0092-8674(00)00086-6.

Abstract

Heterotrimeric G proteins transduce signals from cell surface receptors to modulate the activity of cellular effectors. Src, the product of the first characterized proto-oncogene and the first identified protein tyrosine kinase, plays a critical role in the signal transduction of G protein-coupled receptors. However, the mechanism of biochemical regulation of Src by G proteins is not known. Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src. Galphas and Galphai similarly modulate Hck, another member of Src-family tyrosine kinases. Galphas and Galphai bind to the catalytic domain and change the conformation of Src, leading to increased accessibility of the active site to substrates. These data demonstrate that the Src family tyrosine kinases are direct effectors of G proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Blotting, Western
  • Catalytic Domain
  • Cell Line
  • Down-Regulation
  • Enzyme Activation
  • Fibroblasts
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Kinetics
  • Mice
  • Models, Biological
  • Mutation / genetics
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Conformation
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-hck
  • Signal Transduction
  • src-Family Kinases / chemistry
  • src-Family Kinases / metabolism*

Substances

  • Proto-Oncogene Proteins
  • Phosphotyrosine
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Protein-Tyrosine Kinases
  • HCK protein, human
  • Hck protein, mouse
  • Proto-Oncogene Proteins c-hck
  • src-Family Kinases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gs
  • Heterotrimeric GTP-Binding Proteins